The Lush Black Box Prize offers, in any one year, the full £250,000 Lush Prize fund for a key breakthrough in human toxicity pathways research. It is called the Black Box Prize because traditional product safety testing, relying on animal tests, explains little about whether and how chemicals cause adverse health effects in humans: it treats the issue as a ‘black box’. Lush wants to help open the box and improve the science of safety testing.
The aim of the Black Box Prize is to stimulate a worldwide research and training focus on human toxicity pathways, with the accompanying development of human biology-based assays and of the computational tools (e.g. systems biology approaches, physiologically-based pharmacokinetic models and in vitro-in vivo extrapolation techniques) needed to replace the use of animals in toxicology.
This would drive forward the 21st-century culture change in the world of toxicology research and training which has already started as a result of the U.S. National Research Council’s 2007 report.
21st-Century Toxicology and toxicity pathways
21st-Century Toxicology is so called because it applies novel and emerging techniques and models developed in this century, such as the ’omics (such as genomics, transcriptomics, proteomics), human induced pluripotent stem cells, three-dimensional human tissue models, high-content analysis microscopy, microfluidics (e.g. labs-on-chips) and systems biology (the computational interpretation, integration and modelling of experimental data – molecular, cellular, tissue, etc. – to create understanding of complex biological processes at the whole organism level).
Microfluidic devices can be used to study
human cells with speed, precision and reproducibility
A transformation in toxicology has been unfolding since the publication of the U.S. National Research Council’s 2007 report. This recommended a “21st-century paradigm” for safety testing, involving a radical move away from studying apical endpoints in animal tests towards a completely new framework based on understanding toxicity pathways within human cells.
A toxicity pathway is defined as the cellular chain of events that follow when a toxic chemical first interacts with cells in the body, such as by a receptor interaction or through DNA binding – known as the molecular initiating event. Toxicity pathways represent adverse perturbations of normal cell pathways, resulting in changes in gene function, cell signalling or protein production, and affecting the health and function of the cells (e.g. membrane changes, oxidative stress). The eventual result is seen as a toxic effect (or adverse health outcome) in the whole organism, such as when a chemical carcinogen causes a tumour. Although most toxic effects ultimately involve a complex interplay of different tissues, organs and body systems, toxicity pathways research focuses on the early events at the molecular and cellular levels.
Key toxicity pathways are being elucidated using computational models and human-specific molecular and cellular studies in the test tube, with the aid of systems biology tools. Assays can be developed which identify whether or not chemicals trigger these pathways and eventually lead to toxic effects.
21st-Century Toxicology offers dramatic advantages over traditional animal testing: speed, human relevance, cost-effectiveness, understanding the causes of toxicity, predicting human variability and effects at different life stages (e.g. infants, children, adults), testing chemical mixtures; and the replacement of animal testing, which causes suffering to many thousands of animals every year.
There are expected to be hundreds of toxicity pathways, variously associated with different cells (e.g. skin, liver, kidney, nervous system) in the body and with different classes of chemicals. A single chemical may activate several such pathways, but there is probably a smaller core of cellular events that will provide the key targets for new safety tests. A full elucidation of some toxicity pathways is very close, for example for direct carcinogens and for skin sensitising chemicals.
Research is eligible for the Black Box Prize if it fully elucidates and describes a human toxicity pathway, with experimental evidence to demonstrate all the links from the first interaction of one or more chemical molecules to the full effects at the cellular level. The research should have been completed and published within three years prior to the annual award.
If you would like to discuss this area of the Prize further please contact us rather than using a nomination form.